title: Effects of salubrinal on development of osteoclasts and osteoblasts from bone marrow-derived cells.
abstract: BACKGROUND
  Osteoporosis is a skeletal disease leading to an increased risk of bone fracture. Using a mouse osteoporosis model induced by administration of a receptor activator of nuclear factor kappa-B ligand (RANKL), salubrinal was recently reported as a potential therapeutic agent. To evaluate the role of salubrinal in cellular fates as well as migratory and adhesive functions of osteoclast/osteoblast precursors, we examined the development of primary bone marrow-derived cells in the presence and absence of salubrinal. We addressed a question: are salubrinal's actions more potent to the cells isolated from the osteoporotic mice than those isolated from the control mice?
  
  
  METHODS
  Using the RANKL-injected and control mice, bone marrow-derived cells were harvested. Osteoclastogenesis was induced by macrophage-colony stimulating factor and RANKL, while osteoblastogenesis was driven by dexamethasone, ascorbic acid, and β-glycerophosphate.
  
  
  RESULTS
  The results revealed that salubrinal suppressed the numbers of colony forming-unit (CFU)-granulocyte/macrophages and CFU-macrophages, as well as formation of mature osteoclasts in a dosage-dependent manner. Salubrinal also suppressed migration and adhesion of pre-osteoclasts and increased the number of CFU-osteoblasts. Salubrinal was more effective in exerting its effects in the cells isolated from the RANKL-injected mice than the control. Consistent with cellular fates and functions, salubrinal reduced the expression of nuclear factor of activated T cells c1 (NFATc1) as well as tartrate-resistant acid phosphatase.
  
  
  CONCLUSIONS
  The results support the notion that salubrinal exhibits significant inhibition of osteoclastogenesis as well as stimulation of osteoblastogenesis in bone marrow-derived cells, and its efficacy is enhanced in the cells harvested from the osteoporotic bone samples.
authors.affiliation: Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN 46202, USA. hyokota@iupui.edu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hamamura
authors.forename: Andy
authors.initials: A
authors.lastname: Chen
authors.forename: Todd R
authors.initials: TR
authors.lastname: Dodge
authors.forename: Nancy
authors.initials: N
authors.lastname: Tanjung
authors.forename: Aysan
authors.initials: A
authors.lastname: Abedinpoor
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy; D013234:Stem Cells / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D002934:Cinnamates; C496827:salubrinal; D013890:Thiourea